Cold‐inducible RNA‐binding protein contributes to tissue remodeling in chronic rhinosinusitis with nasal polyps

• Published in: Allergy (Copenhagen) Vol. 76; no. 2; pp. 497 - 509
• Main Authors: Shi, Li‐Li, Ma, Jin, Deng, Yi‐Ke, Chen, Cai‐Ling, Wang, Heng, Cao, Ping‐Ping, Long, Xiao‐Bo, Zeng, Ming, Liu, Zheng
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.02.2021
• Subjects: Advanced glycosylation end products; Allergies; Blocking antibodies; Cell differentiation; Chronic Disease; chronic rhinosinusitis with nasal polyps; cold‐inducible RNA‐binding protein; Edema; Enzyme-linked immunosorbent assay; epithelial cell; Epithelial cells; Gelatinase A; Gelatinase B; Glycosylation; Hay fever; Humans; Immunohistochemistry; Inflammation; Leukocytes (eosinophilic); Lipopolysaccharides; macrophage; Macrophages; Matrilysin; Matrix metalloproteinase; Monocytes; Mucosa; Nasal Polyps; Polyps; Rhinitis; Rhinosinusitis; Ribonucleic acid; RNA; RNA-Binding Proteins; Secretions; Sinusitis; Toll-like receptors; Tumor necrosis factor; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; macrophage; matrix metalloproteinase; epithelial cell; chronic rhinosinusitis with nasal polyps; cold-inducible RNA-binding protein
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.14287

Background Cold‐inducible RNA‐binding protein (CIRP) is a newly identified damage‐associated molecular pattern molecule. Its roles beyond promoting inflammation and in human diseases are poorly understood. This study aimed to investigate the involvement of CIRP in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods Immunohistochemistry, quantitative RT‐PCR, and ELISA were used to detect the expression of CIRP and matrix metalloproteinases (MMPs) in sinonasal mucosal samples and nasal secretions. Human nasal epithelial cells (HNECs) and THP‐1 cells, a human monocytic/macrophage cell line, were cultured to explore the regulation of CIRP expression and MMP expression. Results Cytoplasmic CIRP expression in nasal epithelial cells and CD68+ macrophages in sinonasal tissues, and CIRP levels in nasal secretions were significantly increased in both patients with eosinophilic and noneosinophilic CRSwNP as compared to those in control subjects. IL‐4, IL‐13, IL‐10, IL‐17A, TNF‐α, Dermatophagoides pteronyssinus group 1, and lipopolysaccharide induced the production and secretion of CIRP from HNECs and macrophages differentiated from THP‐1 cells. CIRP promoted MMP2, MMP7, MMP9, MMP12, and vascular endothelial growth factor A (VEGF‐A) production from HNECs, macrophages differentiated from THP‐1 cells, and polyp tissues, which was inhibited by the blocking antibody for Toll‐like receptor 4, but not advanced glycation end products. The expression of MMPs and VEGF‐A in tissues correlated with CIRP levels in nasal secretions in patients with CRSwNP. Conclusions The upregulated production and release of CIRP from nasal epithelial cells and macrophages may contribute to the edema formation in both eosinophilic and noneosinophilic CRSwNP by inducing MMP and VEGF‐A production from epithelial cells and macrophages. Expression of CIRP in sinonasal tissues and nasal secretions is significantly increased in both patients with eosinophilic and non‐eosinophilic CRSwNP. TNF‐α, LPS, Der p1, IL‐4, IL‐13, IL‐17A, and IL‐10 induce the production and secretion of CIRP from nasal epithelial cells and macrophages. The elevated CIRP then promotes MMP and VEGF‐A production from macrophages and nasal epithelial cells via TLR4, and therefore contributes to the edema formation in both eosinophilic and non‐eosinophilic nasal polyps. Abbreviations: CIRP, cold‐inducible RNA‐binding protein; CRSwNP, chronic rhinosinusitis with nasal polyps; Der p1, Dermatophagoides pteronyssinus group 1; ECM, extracellular matrix; LPS, lipopolysaccharide; MMP, matrix metalloproteinase; TLR4, Toll‐like receptor 4; TIMP, tissue metallopeptidase inhibitor; TNF‐α, tumor necrosis factor‐α; VEGF‐A, vascular endothelial growth factor‐A.